Assumptions and contradictions in measles and measles immunization research: Is measles good for something?

Measles infection, the major cause of childhood mortality among infections preventable by immunization, has been considered to kill mainly young and malnourished children. Assuming that mainly 'weak' children are saved by immunizations, it has been speculated that the impact on survival of immunization is likely to be limited because the malnourished children are more prone to die of other infections. However, recent studies from developing countries have suggested that host factors may not be the most important determinants of acute and long-term mortality after measles infection. Instead, it was found that infection contracted after exposure at home is associated with much higher mortality than infection contracted from someone outside the home. Furthermore, measles is particularly severe if contracted from someone of the opposite sex. Hence, transmission factors, in particularly intensity of exposure and cross-sex transmission, may be more important determinants of measles mortality than the host factors usually emphasized. Consistent with these observations and in contrast to assumptions about 'weak' children dying, immunization is associated with a major reduction in mortality. Since measles immunization is associated with a 30% reduction in mortality or more, the impact is much larger than should be expected from the proportion of all deaths attributed to measles. It has therefore been suggested that measles immunization may prevent the persistent immunosuppression and delayed mortality assumed to be associated with measles. However, several observations contradict the common understanding that the function of measles immunization is only to prevent the acute and long-term mortality associated with measles infection. Recently, the high-titre measles immunization recommended by WHO was found to be associated with reduced survival for female recipients compared with girls who had received the standard low-dose measles vaccine, and this difference in survival was not due to suboptimal protection against measles infection. Contrary to usual assumptions, standard low-dose measles vaccine reduces mortality even more when given before 9 months of age, the age currently recommended by WHO. The beneficial impact of standard vaccine is apparently temporary, lasting 1 to 2 years, whereas it should increase with the age of the child. The beneficial effect seems to be particularly strong for girls. The most likely interpretation of these observations, is that standard low-dose measles vaccine has a non-specific beneficial effect. Contrary to current assumptions, children who survive the acute phase of measles infection may have a survival advantage compared with unimmunized, uninfected children. Hence, both disease and immunization may be associated with non-specific beneficial effects, presumably due to some form of immunostimulation. In this perspective, the problem of high-titre immunization was apparently not that the vaccine was immunosuppressive, but that it may have lacked the non-specific beneficial impact of standard vaccine. Should these observations be reproducable, they question the culture of 'eradication' and have major implications for future immunization policies.